The major objective of the present investigation is to elucidate the importance of membrane-related events (depolarization and calcium entry) in skeletal metabolism. Tissue culture techniques will be employed to examine the effects of membrane-active agents on hormonal and nonhormonal-induced alterations in bone resorption and bone formation (collagen synthesis). Particular objectives are as follows: 1. To elucidate the importance of depolarization in skeletal metabolism by employing membrane stabilizers (local anesthetics, propranolol, diphenylhydantoin) to alter bone resorption and formation. 2. To reveal the role of calcium transport in bone remodeing by utilizing drugs capable of affecting this phenomenon, i.e., membrane stabilizers, ionophores and calcium antagonists to alter bone resorption and collagen synthesis. 3. To determine the importnce of cyclic AMP in skeletal remodeling and to reveal the influence of depolarization and/or calcium transport on cyclic AMP formation. 4. To elucidate the significance of hyaluronic acid in bone resorption and the effects of membrane-stabilizers on hyaluronate synthesis. 5. To examine the possible involvement of cyclic GMP in skeletal metabolism. 6. To determine the effects of membrane-active agents on calcitonin-induced inhibition of PTH-stimulated resorption, especially the effects on the transient nature of this inhibition ("escape"). 7. To explain clinical findings of diphenylhydantoin- and propranolol-induced alterations in serum calcium and bone metabolism.